Trifluoroacetic acid → HCID 86683826, compound

HRID 1261432Notes

Reaction equation

HRID 1261432 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16](=[CH2:27])[CH2:17][CH2:18][NH:19]C(OC(C)(C)C)=O)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:28])[CH:11]=2)[CH:6]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16](=[CH2:27])[CH2:17][CH2:18][NH2:19])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:28])[CH:11]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86683827HCID 86683827, compound

Product 1

HCID 86683826HCID 86683826, compoundYield 83.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [4-(3-tert-butoxycarbonylamino-1-methylene-propyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (0.79 g, 2.0 mmol) in methylene chloride (28.5 mL) was added trifluoroacetic acid (7.5 mL, 98 mmol). The reaction mixture was stirred at room temperature for 4 hours. The solvent was removed under vacuum and the resulting brown residue was dissolved in toluene. The solvent was again removed under vacuum, then dissolved in methylene chloride (−5 mL) with heating. The mixture was diluted with hexanes (˜10 mL). As a result, some oil precipitated. The mixture was diluted with dichloromethane and the dark brown solution was stored in the refrigerator for 15 hours; however, further precipitation of the product was not successful. The solvent was removed and the crude mixture (1.1 g) was purified using flash chromatography (80 g ISCO column, 0-100% methylene chloride in hexanes followed by 0-20% methanol in methylene chloride) to afford [4-(3-amino-1-methylene-propyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (0.502 g, 75%) as a white, amorphous, and hygroscopic solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.64-7.71 (m, 1H), 7.55-7.59 (m, 1H), 7.32-7.38 (m, 1H), 7.16 (td, J=8.5, 2.3 Hz, 1H), 5.53 (s, 1H), 5.09 (s, 1H), 3.77-3.81 (m, 2H), 3.67-3.71 (m, 4H), 2.99 (d, J=6.0 Hz, 2H), 2.65 (t, J=7.4 Hz, 2H), 2.28 (s, 4H).

Workup

  1. customThe solvent was removed under vacuum
  2. dissolutionthe resulting brown residue was dissolved in toluene
  3. customThe solvent was again removed under vacuum
  4. dissolutiondissolved in methylene chloride (−5 mL)
  5. temperaturewith heating
  6. additionThe mixture was diluted with hexanes (˜10 mL)
  7. customAs a result, some oil precipitated
  8. additionThe mixture was diluted with dichloromethane
  9. waitthe dark brown solution was stored in the refrigerator for 15 hours
  10. customhowever, further precipitation of the product
  11. customThe solvent was removed
  12. customthe crude mixture (1.1 g) was purified

Sources & evidence

ORD record
ord-46e28bcad9cd460f81b14010e3e249e3
Source dataset
uspto-grants-2013_06
Patent number
US08470884B2

Reaction notes

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